Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol 130, 244-251

The Hart and Louis Laboratory, Clinical Immunology and Allergy, Department of Medicine, UCLA David Geffen School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
Clinical Immunology (Impact Factor: 3.67). 03/2009; 130(3):244-251. DOI: 10.1016/j.clim.2008.10.007


BackgroundCellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals.ObjectiveWe conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects.MethodsStudy subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing.ResultsAll subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 g broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts.ConclusionOral sulforaphane safely and effectively induces mucosal Phase II enzyme expression in the upper airway of human subjects. This study demonstrates the potential of antioxidant Phase II enzymes induction in the human airway as a strategy to reduce the inflammatory effects of oxidative stress.Clinical implicationsThis study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease.Capsule summaryA placebo-controlled dose escalation trial demonstrated that naturally occurring sulforaphane from broccoli sprouts can induce a potent increase in antioxidant Phase II enzymes in airway cells.

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    • "Broccoli, glucoraphanin, and sulforaphane, Nutrition (2015), http:// HO-1 [42] and jejunal enterocyte expression of GST [9] in humans. The observations that sulforaphane down-regulates the expression of the phase 1 enzymes, cytochrome P450 (CYP), family 3, subfamily A, polypeptide 4 (CYP3 A4, a major deactivator of pharmaceutical drugs [43]), CYP, family 4, subfamily A isozymes (CYP4 A isozymes, convert arachidonic acid to vasoconstricting 19-and 20-hydroxyeicosatetraenoic acids [44]), and epoxide hydrolase (converts vasodilating epoxyeicosatetraenoic acid metabolites of arachidonic acid into inactive dihydroxy-eicosatrienoic acids [44]), while up-regulating the expression of phase 2 GST, NQO1, and GPx2 [31], is consistent with the hypothesis that sulforaphane potentiates the phase 2 system while attenuating the phase 1 system [44] [45]. "
    Nutrition 03/2015; 31(9). DOI:10.1016/j.nut.2015.03.003 · 2.93 Impact Factor
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    • "Declining Nrf2 activity may also be involved in the deleterious neurocognitive decline associated with aging [8] [9] [10]. The broccoli-derived bioactive sulforaphane (SFN) elicits activation of the Nrf2 antioxidant pathway, which protects tissues from toxic and carcinogenic insult by promoting transcription of genes containing the antioxidant response element (ARE) [11] [12] [13]. Because of the cytoprotective nature of Nrf2, activation of the Nrf2 pathway may be a good therapeutic target for reducing oxidative and immune stress associated with chronic low-grade inflammation. "
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    ABSTRACT: Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. SFN increases antioxidant enzymes including NAD(P)H quinone oxidoreductase (NQO1) and heme oxygenase I (HMOX1) and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days prior to an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 h following LPS, and mRNA quantified in liver and brain at 24 h. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin (IL)-1β expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. Additionally, IL-1β was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 β, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS.
    Nutrition Research 11/2014; 34(11). DOI:10.1016/j.nutres.2014.10.001 · 2.47 Impact Factor
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    • "Our stability studies using LC- MS indicate that SF is stable in water at room temperature for at least 5 days. Also, several studies have indicated that SF is bioavailable in both human and animal models [41] [42]. "
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    ABSTRACT: Background. We investigated the effects of sulforaphane (SF), the main active isothiocyanate in cruciferous vegetables, on arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as models. Methods. Rats were treated for 8 weeks with either drinking water alone (control) or SF (20 or 40 mg/kg) added to drinking water. Mean arterial pressure (MAP) was measured at 7-day intervals throughout the study. At the end of treatment rats were euthanized, and kidneys were harvested to prepare microsomes and measure enzymes involved in regulation of vasoactive metabolites: CYP4A, the key enzyme in the formation of 20-hydroxyeicosatetraenoic acid, and the soluble epoxide hydrolase, which is responsible for the degradation of the vasodilator metabolites such as epoxyeicosatetraenoic acids. Effect of SF on kidney expression of CYP4A was investigated by immunoblotting. Results. We found that treatment with SF leads to significant reductions in both, the expression and activity of renal CYP4A isozymes, as well as the activity of soluble epoxide hydrolase (sEH). Consistent with these data, we have found that treatment with SF resisted the progressive rise in MAP in the developing SHR in a dose-dependent manner. Conclusion. This is the first demonstration that SF modulates the metabolism of AA by both P450 enzymes and sEH in SHR rats. This may represent a novel mechanism by which SF protects SHR rats against the progressive rise in blood pressure.
    03/2014; 2014(8):683508. DOI:10.1155/2014/683508
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